Early detection versus prevention in colorectal cancer screening: Methods estimates and public health implications

Abstract

Flexible sigmoidoscopy (FS) screening has been shown to reduce both the incidence and mortality of colorectal cancer (CRC) in 4 large-scale randomized controlled trials (RCTs). [1][2][3][4][5] The article by Doroudi et al 6 in this issue of Cancer provides in-depth analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial for CRC screening. Between 1993 and 2001, PLCO randomized 154,900 men and women aged 55 to 74 years to either an intervention arm (FS screening at baseline and at 3 or 5 years) or usual-care arm. After 13 years of follow-up in both the intervention and usual-care arms, 1008 CRC cases in the intervention arm and 1291 CRC cases in the usual-care arm were observed.The 13-year survival rates in the intervention and usual-care arms were significantly different for cases of distal CRC (77% in the intervention arm vs 66% in the usual-care arm; P<.0001), whereas they were not for all CRC (68% vs 66%, respectively; P 5 .16) and for proximal CRC cases. Anatomic location and stage distribution by trial arm and CRCspecific survival by reason of detection also are reported by Doroudi et al. 6 Moreover, whether mortality reduction in the intervention arm was due primarily to the early detection of CRC or to prevention via removal of adenomatous polyps was investigated. Overall, 29% to 35% of averted CRC deaths were estimated to be due to early detection and 65% to 71% were estimated to be due to prevention.We believe the idea in the study by Doroudi et al 6 to assess the percentage of mortality reduction due to prevention via the removal of adenomatous polyps or to early detection is brilliant. As stated by the authors, "This assessment is of importance because it will enhance the scientific understanding of how FS screening prevents CRC deaths and may further inform future CRC screening recommendations." 6 Nevertheless, the authors have adopted an analytic approach in which the use of comparison of survivals in the intervention and usual-care arms is flawed by lead time, which inflates the estimate of survival in the intervention arm. Moreover, when comparing survivals in the 2 arms of the PLCO trial (in which intention-to-treat results are reported), other main factors can improve the point estimate of survival in the intervention arm, namely: 1) better access to treatment that would increase survival; it most likely is not the case because the intervention and usual-care arms of the PLCO trial were sampled within the same health maintenance organizations; 2) overdiagnosis, which is intrinsic to cancer screening; and 3) the sensitivity of the test and the compliance with screening, affecting the percentage of screen-detected cancers.The use of survival in the intervention arm should be avoided. On the contrary, either survival, as Doroudi et al proposed, 6 or the fatality rate (FR) in the control arm, which are not affected by the lead time, permit the correct estimation of the mortality reduction due to the early detection of CRC or to prevention via the removal of adenomatous p...